To take advantage of the advances in sequencing genomes of malaria parasites large-scale analyses of protein-protein interactions and gene expression profiles will be essential. As a part of the Malaria Genome Project, 5X coverage of a rodent malaria parasite Plasmodium yoelii genome has been accomplished by the Institute for Genomic Research (TIGR), and a large collection of cDNA clones have been sequenced. With these reagents in hand, we propose to establish reagents to undertake high throughput yeast two hybrid screening to assess protein-protein interactions. Our experience with yeast two-hybrid system suggests that, for reasons that are not entirely clear, P. yoelii genes are better expressed in the yeast compared to P. falciparum. By using the power of yeast genetics, the protocols proposed here will permit screening for interacting proteins with much greater efficiency. We also propose to construct cDNA microarrays using the sequenced P. yoelii clones for undertaking large-scale gene expression profiling. Again, the rodent malaria model will provide certain advantage in conducting gene expression profiling of parasites replicating in vivo. A variety of investigations will be aided by availability of such microarrays.